The structure and function of the major connective tissue macromolecules, the collagens and glycoconjugates, are being examined in animal models and human diseases. The extracellular matrix macromolecules present in cornea, sclera, trabecular meshwork, vitreous, choroid and Bruch's membrane are fractionated and characterized directly using biochemical procedures. Alternatively, samples of these tissues are radiolabeled in organ culture, or cells derived from these tissues are grown and labeled in cell culture. The macromolecular products synthesized by these cultures are similarly characterized. Alterations in the normal composition of collagens, glycoproteins and proteoglycans may accompany or even be the basis for certain visually disabling ocular diseases. Keratoconus corneas secrete metalloenzymes active against type IV collagen as well as type I collagenase. Inhibitors of these degradative enzymes are being tested.